Oxygen sensing is important in metabolism and many disease-related processes, such as hypoxia and angiogenesis. The goal of this project is to study the mechanisms of and neurons involved in oxygen sensing in C. elegans. C. elegans serves as an excellent model system because it is a simple multicellular organism with powerful molecular and genetic tools available. However, current approaches for C. elegans behavior research limit the type of experiments that can be performed and the interpretation of some results due to technical difficulties. Microfluidics lends itself in solving these technical challenges and can advance these studies with quantitative assessment of behaviors. In this project, reliable microfluidic oxygen delivery systems that assay worms' response to specific oxygen concentrations or gradients will be developed. Appropriate mathematical models to design these devices will be used, and microfabrication processes using biocompatible and oxygen permeable polymer materials will be explored. These tools allow the quantitative investigation of the neural circuitry using mutants that lack specific functions in four potentially important sensory neurons. The assay will probe whether and how these neurons define the specificity of oxygen preference. Furthermore, this study will elucidate whether oxygen preference is an adaptable process during which the organism may change its metabolism in accordance with the environment. The roles of a class of guanylyl cyclases in sensing and behaviors will also be studied as well as possible connections to the classical transcriptional pathways. This type of analysis is only possible with a finely controlled oxygen delivery system. The general techniques developed in this study should impact other C. elegans researches of sensing and behaviors such as odor discrimination and thermo-sensation.